Novel substituted benzothiazole and Imidazo[2,1b][1,3,4]Thiadiazole derivatives: Synthesis, characterization, molecular docking study, and investigation of their in vitro antileishmanial and antibacterial activities
| Autor: | Mustafa Er, Tuncay Karakurt, Hakan Tahtaci, Şahin Direkel, Arif Özer |
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| Přispěvatelé: | Belirlenecek, Kırşehir Ahi Evran Üniversitesi, Fen-Edebiyat Fakültesi, Kimya Bölümü |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
HOMO
Nitrile 010405 organic chemistry Chemistry Biological activity Organic Chemistry Phenacyl bromide Carbon-13 NMR Benzothiazole 010402 general chemistry 01 natural sciences Medicinal chemistry 0104 chemical sciences Analytical Chemistry Inorganic Chemistry chemistry.chemical_compound Docking (molecular) Molecular docking Trifluoroacetic acid Proton NMR Antibacterial activity Spectroscopy Imidazo[2 1-b][1 3 4]thiadiazole |
| Popis: | Karakurt, Tuncay/0000-0001-6944-9883; TAHTACI, HAKAN/0000-0002-1557-6315 WOS: 000471778600031 In this study, we synthesized new imidazo[2,1-b][1,3,4]thiadiazole derivatives containing benzothiazole group. To this end, we firstly obtained the benzo[d]thiazol-2-ylthio/oxy acetonitrile compounds (3a,b), the starting materials, in high yields (82% and 87%, respectively). Then, we synthesized the 2-amino-1,3,4-thiadiazole derivatives (4a,b) from the reaction of these nitrile derivatives (3a,b) with thio-semicarbazide in trifluoroacetic acid (TFA) (in yields of 83% and 84%). Finally, we synthesized the imidazo [2,1-b][1,3,4]thiadiazole derivatives (5-24) containing benzothiazole group, which are the target compounds, from reactions of 2-amino-1,3,4-thiadiazole derivatives (4a,b) with phenacyl bromide derivatives (in yields of 53%-73%). All of the compounds synthesized were characterized with H-1 NMR, C-13 NMR, FT-IR, elemental analysis, and mass spectroscopy. Antileishmanial and antibacterial activity tests were applied to the compounds synthesized in the study. It was observed that compound 8 had the highest antileishmanial activity (MIC = 10 000 mu g/mL). Also, compounds 7 and 17 were found to be effective at the highest concentration studied (MIC = 20 000 mu g/mL). In terms of antibacterial activity, compounds 4b and 7 were found to be the most effective compounds against Escherichia coli (MIC = 625 mu g/mL). Theoretical calculations were performed to support the experimental results. To this end, we performed Molecular Docking studies to determine whether or not the compounds (4a, 4b, 7 and 13) optimized with Gaussian09 using the DET/B3LYP/6-31G(d,p) theory, which is a quantum chemical calculation, could be an inhibitor agent for the 2eg7 Escherichia coli protein structure. Also, we investigated the relationship between the calculated HOMO values of these four ligands and docking studies. (C) 2019 Elsevier B.V. All rights reserved. Karabuk UniversityKarabuk University [KBUBAP-17-YL-038] The financial support by the Karabuk University (Project ID Number: KBUBAP-17-YL-038) is gratefully acknowledged. |
| Databáze: | OpenAIRE |
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